tbuckley/cabot-search huggingface dataset:
3D-Stacked Multistage Inertial Microfluidic Chip for High-Throughput Enrichment of Circulating Tumor Cells
Authors: X. Xu, X. Huang, J. Sun, J. Chen, G. Wu, Y. Yao, N. Zhou, S. Wang, L. Sun
Journal: Cyborg and Bionic Systems (2022)

Whether for cancer diagnosis or single-cell analysis, it remains a major challenge to isolate the target sample cells from a large background cell for high-efficiency downstream detection and analysis in an integrated chip. Therefore, in this paper, we propose a 3D-stacked multistage inertial microfluidic sorting chip for high-throughput enrichment of circulating tumor cells (CTCs) and convenient downstream analysis. In this chip, the first stage is a spiral channel with a trapezoidal cross-section, which has better separation performance than a spiral channel with a rectangular cross-section. The second and third stages adopt symmetrical square serpentine channels with different rectangular cross-section widths for further separation and enrichment of sample cells reducing the outlet flow rate for easier downstream detection and analysis. The multistage channel can separate 5 μ m and 15 μ m particles with a separation efficiency of 92.37% and purity of 98.10% at a high inlet flow rate of 1.3 mL/min. Meanwhile, it can separate tumor cells (SW480, A549, and Caki-1) from massive red blood cells (RBCs) with a separation efficiency of &gt;80%, separation purity of &gt;90%, and a concentration fold of ~20. The proposed work is aimed at providing a high-throughput sample processing system that can be easily integrated with flowing sample detection methods for rapid CTC analysis.
Author Correction: Transcriptional regulation of N6-methyladenosine orchestrates sex-dimorphic metabolic traits
Authors: David A. Salisbury, David Casero, Zhengyi Zhang, Dan Wang, Jason Kim, Xiaohui Wu, Laurent Vergnes, Aashiq H. Mirza, Paola Leon-Mimila, Kevin J. Williams, Adriana Huertas-Vazquez, Samie R. Jaffrey, Karen Reue, Jianjun Chen, Tamer Sallam
Journal: Nature Metabolism (2022)
Prognostic significance of obstructive coronary artery disease in patients admitted with acute decompensated heart failure: the <scp>ARIC</scp> study community surveillance
Authors: Zainali S. Chunawala, Arman Qamar, Sameer Arora, Ambarish Pandey, Marat Fudim, Muthiah Vaduganathan, Robert J. Mentz, Deepak L. Bhatt, Melissa C. Caughey
Journal: European Journal of Heart Failure (2022)
Microsatellite Instability–High Endometrial Cancers with <i>MLH1</i> Promoter Hypermethylation Have Distinct Molecular and Clinical Profiles
Authors: Beryl L. Manning-Geist, Ying L. Liu, Kelly A. Devereaux, Arnaud Da Cruz Paula, Qin C. Zhou, Weining Ma, Pier Selenica, Ozge Ceyhan-Birsoy, Lea A. Moukarzel, Timothy Hoang, Sushmita Gordhandas, Maria M. Rubinstein, Claire F. Friedman, Carol Aghajanian, Nadeem R. Abu-Rustum, Zsofia K. Stadler, Jorge S. Reis-Filho, Alexia Iasonos, Dmitriy Zamarin, Lora H. Ellenson, Yulia Lakhman, Diana L. Mandelker, Britta Weigelt
Journal: Clinical Cancer Research (2022)

Abstract Purpose: Microsatellite instability–high (MSI-H) endometrial carcinomas are underpinned by distinct mechanisms of DNA mismatch repair deficiency (MMR-D). We sought to characterize the clinical and genetic features of MSI-H endometrial cancers harboring germline or somatic mutations in MMR genes or MLH1 promoter hypermethylation (MLH1ph). Experimental Design: Of &amp;gt; 1,100 patients with endometrial cancer that underwent clinical tumor-normal sequencing, 184 had MSI-H endometrial cancers due to somatic MMR mutations or MLH1ph, or harbored pathogenic germline MMR mutations. Clinicopathologic features, mutational landscape, and tumor-infiltrating lymphocyte (TIL) scores were compared among MMR-D groups using nonparametric tests. Log-rank tests were used for categorical associations; Kaplan–Meier method and Wald test based on Cox proportional hazards models were employed for continuous variables and survival analyses. Results: Compared with patients with germline (n = 25) and somatic (n = 39) mutations, patients with MLH1ph endometrial cancers (n = 120) were older (P &amp;lt; 0.001), more obese (P = 0.001) and had more advanced disease at diagnosis (P = 0.025). MLH1ph endometrial cancers were enriched for JAK1 somatic mutations as opposed to germline MMR-D endometrial cancers which showed enrichment for pathogenic ERBB2 mutations. MLH1ph endometrial cancers exhibited lower tumor mutational burden and TIL scores compared with endometrial cancers harboring germline or somatic MMR mutations (P &amp;lt; 0.01). MLH1ph endometrial cancer patients had shorter progression-free survival (PFS) on univariate analysis, but in multivariable models, stage at diagnosis remained the only predictor of survival. For stage I/II endometrial cancer, two-year PFS was inferior for patients with MLH1ph endometrial cancers compared with germline and somatic MMR groups (70% vs. 100%, respectively). Conclusions: MLH1ph endometrial cancers likely constitute a distinct clinicopathologic entity compared with germline and somatic MMR-D ECs with potential treatment implications.
Under-representation of female athletes in research informing influential concussion consensus and position statements: an evidence review and synthesis
Authors: Christopher D'Lauro, Emily Ruth Jones, Lily MC Swope, Melissa N Anderson, Steven Broglio, Julianne D Schmidt
Journal: British Journal of Sports Medicine (2022)

Objective We aimed to quantify the female athlete composition of the research data informing the most influential consensus and position statements in treating sports-related concussions. Design We identified the most influential concussion consensus and position statements through citation and documented clinician use; then, we analysed the percentage of male and female athletes from each statement’s cited research. Data sources We searched PubMed on 26 August 2021 with no date restrictions for English language studies using the terms ‘concussion position statement’ and ‘concussion consensus statement.’ Eligibility criteria for selecting studies Based on each statement having multiple statement editions, documented clinician use, and substantial citation advantages, we selected the National Athletic Trainers’ Association (NATA, 2014), International Conference on Concussion in Sport (ICCS, 2017) and the American Medical Society for Sports Medicine (AMSSM, 2019). We extracted all cited studies from all three papers for assessment. For each paper analysing human data, at least two authors independently recorded female athlete participant data. Results A total of 171 distinct studies with human participants were cited by these three consensus and position papers and included in the female athlete analyses (93 NATA; 13 ICCS; 65 AMSSM). All three statements documented a significant under-representation of female athletes in their cited literature, relying on samples that were overall 80.1% male (NATA: 79.9%, ICCS: 87.8 %, AMSSM: 79.4%). Moreover, 40.4% of these studies include no female participants at all. Conclusion Female athletes are significantly under-represented in the studies guiding clinical care for sport-related concussion for a broad array of sports and exercise medicine clinicians. We recommend intentional recruitment and funding of gender diverse participants in concussion studies, suggest authorship teams reflect diverse perspectives, and encourage consensus statements note when cited data under-represent non-male athletes.
Toxicity Profiles of Systemic Therapies for Advanced Hepatocellular Carcinoma
Authors: Christopher D. Griffiths, Betty Zhang, Kasia Tywonek, Brandon M. Meyers, Pablo E. Serrano
Journal: JAMA Network Open (2022)

The recent development of targeted therapy and immunotherapy has made neoadjuvant therapy an attractive option for patients with hepatocellular carcinoma (HCC). However, surgeons are concerned that adverse effects of neoadjuvant therapy with these agents could lead to delayed or even cancelled surgeries.
A Delightful Trip Along the Pathway of Cannabinoid and Endocannabinoid Chemistry and Pharmacology
Authors: Raphael Mechoulam
Journal: The Annual Review of Pharmacology and Toxicology (2022)

After a traumatic childhood in Europe during the Second World War, I found that scientific research in Israel was a pleasure beyond my expectations. Over the last 65 year, I have worked on the chemistry and pharmacology of natural products. During the last few decades, most of my research has been on plant cannabinoids, the endogenous cannabinoids arachidonoyl ethanolamide (anandamide) and 2-arachidonoyl glycerol, and endogenous anandamide-like compounds, all of which are involved in a wide spectrum of physiological reactions. Two plant cannabinoids, Δ9-tetrahydrocannabinol and cannabidiol, are approved drugs. However, the endogenous cannabinoids and the anandamide-like constituents have not yet been well investigated in humans. For me, intellectual freedom-the ability to do research based on my own scientific interests-has been the most satisfying part of my working life. Looking back over the 91 years of my long life, I conclude that I have been lucky, very lucky, both personally and scientifically.
Epigenetic Regulation of Profibrotic Macrophages in Systemic Sclerosis–Associated Interstitial Lung Disease
Authors: Anna Papazoglou, Mengqi Huang, Melissa Bulik, Annika Lafyatis, Tracy Tabib, Christina Morse, John Sembrat, Mauricio Rojas, Eleanor Valenzi, Robert Lafyatis
Journal: Arthritis & Rheumatology (2022)

Systemic sclerosis-associated interstitial lung disease (SSc-ILD) is the leading cause of death in patients with SSc with unclear pathogenesis and limited treatment options. Evidence strongly supports an important role for profibrotic secreted phosphoprotein 1 (SPP1)-expressing macrophages in SSc-ILD. This study was undertaken to define the transcriptome and chromatin structural changes of SPP1 SSc-ILD macrophages in order to better understand their role in promoting fibrosis and to identify transcription factors associated with open chromatin driving their altered phenotype.We performed single-cell RNA sequencing (scRNA-Seq) on 11 explanted SSc-ILD and healthy control lung samples, as well as single-cell assay for transposase-accessible chromatin sequencing on 5 lung samples to define altered chromatin accessibility of SPP1 macrophages. We predicted transcription factors regulating SPP1 macrophages using single-cell regulatory network inference and clustering (SCENIC) and determined transcription factor binding sites associated with global alterations in SPP1 chromatin accessibility using Signac/Seurat.We identified distinct macrophage subpopulations using scRNA-Seq analysis in healthy and SSc-ILD lungs and assessed gene expression changes during the change of healthy control macrophages into SPP1 macrophages. Analysis of open chromatin validated SCENIC predictions, indicating that microphthalmia-associated transcription factor, transcription factor EB, activating transcription factor 6, sterol regulatory element binding transcription factor 1, basic helix-loop-helix family member E40, Kruppel-like factor 6, ETS variant transcription factor 5, and/or members of the activator protein 1 family of transcription factors regulate SPP1 macrophage differentiation.Our findings shed light on the underlying changes in chromatin structure and transcription factor regulation of profibrotic SPP1 macrophages in SSc-ILD. Similar alterations in SPP1 macrophages may underpin fibrosis in other organs involved in SSc and point to novel targets for the treatment of SSc-ILD, specifically targeting profibrotic macrophages.
Clinical Outcomes and Risk Stratification of Early-Stage Melanoma Micrometastases From an International Multicenter Study: Implications for the Management of American Joint Committee on Cancer IIIA Disease
Authors: Marc D. Moncrieff, Serigne N. Lo, Richard A. Scolyer, Martin J. Heaton, Jenny P. Nobes, Andrew P. Snelling, Michael J. Carr, Carolyn Nessim, Ryckie Wade, A. Howard Peach, Rumi Kisyova, Jennifer Mason, Ewan D. Wilson, Grant Nolan, Rowan Pritchard Jones, Iva Johansson, Roger Olofsson Bagge, Lucie J. Wright, Nakul G. Patel, Vernon K. Sondak, John F. Thompson, Jonathan S. Zager
Journal: Journal of Clinical Oncology (2022)

Indications for offering adjuvant systemic therapy for patients with early-stage melanomas with low disease burden sentinel node (SN) micrometastases, namely, American Joint Committee on Cancer (AJCC; eighth edition) stage IIIA disease, are presently controversial. The current study sought to identify high-risk SN-positive AJCC stage IIIA patients who are more likely to derive benefit from adjuvant systemic therapy.Patients were recruited from an intercontinental (Australia/Europe/North America) consortium of nine high-volume cancer centers. All were adult patients with pathologic stage pT1b/pT2a primary cutaneous melanomas who underwent SN biopsy between 2005 and 2020. Patient data, primary tumor and SN characteristics, and survival outcomes were analyzed.Three thousand six hundred seven patients were included. The median follow-up was 34 months. Pairwise disease comparison demonstrated no significant survival difference between N1a and N2a subgroups. Survival analysis identified a SN tumor deposit maximum dimension of 0.3 mm as the optimal cut point for stratifying survival. Five-year disease-specific survival rates were 80.3% and 94.1% for patients with SN metastatic tumor deposits ≥ 0.3 mm and < 0.3 mm, respectively (hazard ratio, 1.26 [1.11 to 1.44]; P < .0001). Similar findings were seen for overall disease-free and distant metastasis-free survival. There were no survival differences between the AJCC IB patients and low-risk (< 0.3 mm) AJCC IIIA patients. The newly identified high-risk (≥ 0.3 mm) subgroup comprised 271 (66.4%) of the AJCC IIIA cohort, whereas only 142 (34.8%) patients had SN tumor deposits > 1 mm in maximum dimension.Patients with AJCC IIIA melanoma with SN tumor deposits ≥ 0.3 mm in maximum dimension are at higher risk of disease progression and may benefit from adjuvant systemic therapy or enrollment into a clinical trial. Patients with SN deposits < 0.3 mm in maximum dimension can be managed similar to their SN-negative, AJCC IB counterparts, thereby avoiding regular radiological surveillance and more intensive follow-up.
Single-shot AAV-vectored vaccine against SARS-CoV-2 with fast and long-lasting immunity
Authors: Fuhua Wu, Shuang Luo, Yongshun Zhang, Yangsen Ou, Hairui Wang, Zhaofei Guo, Chunting He, Shuting Bai, Penghui He, Min Jiang, Xiaoyan Chen, Guangsheng Du, Xun Sun
Journal: Acta Pharmaceutica Sinica B (2022)

Due to the insufficient long-term protection and significant efficacy reduction to new variants of current COVID-19 vaccines, the epidemic prevention and control are still challenging. Here, we employ a capsid and antigen structure engineering (CASE) strategy to manufacture an adeno-associated viral serotype 6-based vaccine (S663V-RBD), which expresses trimeric receptor binding domain (RBD) of spike protein fused with a biological adjuvant RS09. Impressively, the engineered S663V-RBD could rapidly induce a satisfactory RBD-specific IgG titer within 2 weeks and maintain the titer for more than 4 months. Compared to the licensed BBIBP-CorV (Sinopharm, China), a single-dose S663V-RBD induced more endurable and robust immune responses in mice and elicited superior neutralizing antibodies against three typical SARS-CoV-2 pseudoviruses including wild type, C.37 (Lambda) and B.1.617.2 (Delta). More interestingly, the intramuscular injection of S663V-RBD could overcome pre-existing immunity against the capsid. Given its effectiveness, the CASE-based S663V-RBD may provide a new solution for the current and next pandemic.
Cancer depends on fatty acids for ATP production: A possible link between cancer and obesity
Authors: Ho Lee, Sang Myung Woo, Hyonchol Jang, Mingyu Kang, Soo-Youl Kim
Journal: Seminars in Cancer Biology (2022)

Several metabolic pathways for the supply of adenosine triphosphate (ATP) have been proposed; however, the major source of reducing power for ADP in cancer remains unclear. Although glycolysis is the source of ATP in tumors according to the Warburg effect, ATP levels do not differ between cancer cells grown in the presence and absence of glucose. Several theories have been proposed to explain the supply of ATP in cancer, including metabolic reprograming in the tumor microenvironment. However, these theories are based on the production of ATP by the TCA-OxPhos pathway, which is inconsistent with the Warburg effect. We found that blocking fatty acid oxidation (FAO) in the presence of glucose significantly decreased ATP production in various cancer cells. This suggests that cancer cells depend on fatty acids to produce ATP through FAO instead of glycolysis. We observed that cancer cell growth mainly relies on metabolic nutrients and oxygen systemically supplied through the bloodstream instead of metabolic reprogramming. In a spontaneous mouse tumor model (KrasG12D; Pdx1-cre), tumor growth was 2-fold higher in mice fed a high-fat diet (low-carbo diet) that caused obesity, whereas a calorie-balanced, low-fat diet (high-carbo diet) inhibited tumor growth by 3-fold compared with that in mice fed a control/normal diet. This 5-fold difference in tumor growth between mice fed low-fat and high-fat diets suggests that fat-induced obesity promotes cancer growth, and tumor growth depends on fatty acids as the primary source of energy.
Long-term follow-up of cladribine treatment in hairy cell leukemia: 30-year experience in a multicentric Italian study
Authors: Livio Pagano, Marianna Criscuolo, Alessandro Broccoli, Alfonso Piciocchi, Marzia Varettoni, Eugenio Galli, Antonella Anastasia, Maria Cantonetti, Livio Trentin, Sofia Kovalchuk, Lorella Orsucci, Annamaria Frustaci, Angelica Spolzino, Stefano Volpetti, Ombretta Annibali, Sergio Storti, Caterina Stelitano, Francesco Marchesi, Massimo Offidani, Beatrice Casadei, Maria Elena Nizzoli, Maria Lucia De Luca, Luana Fianchi, Marina Motta, Luca Guarnera, Edoardo Simonetti, Andrea Visentin, Francesco Vassallo, Marina Deodato, Chiara Sarlo, Attilio Olivieri, Brunangelo Falini, Alessandro Pulsoni, Enrico Tiacci, Pier Luigi Zinzani
Journal: Blood Cancer Journal (2022)

Hairy cell leukemia (HCL) is a rare lymphoproliferative disease with an excellent prognosis after treatment with cladribine (2CDA), although relapse may occur during follow-up. The aim of the study is to review the efficacy, safety, long-term remission rate, and overall survival (OS) in those patients who received 2CDA as first-line treatment. We retrospectively reviewed data of HCL patients treated with 2CDA between March 1991 and May 2019 at 18 Italian Hematological centers: 513 patients were evaluable for study purpose. The median age was 54 years (range 24-88) and ECOG was 0 in 84.9% of cases. A total of 330 (64.3%) patients received 2CDA intravenously and 183 (35.7%) subcutaneously. ORR was 91.8%: CR was obtained in 335 patients (65.3%), PR in 96 (18.7%), and hematological response in 40 (7.8%) patients; in 42 (8.2%) no response was observed. Hemoglobin value (p = 0.044), frequency of circulating hairy cells (p = 0.039), recovery of absolute neutrophil count (p = 0.006), and normalization of spleen (p ≤ 0.001) were associated with CR compared to PR in univariable analysis. At a median follow-up of 6.83 years (range 0.04-28.52), the median time to relapse was 12.2 years. A significant difference in duration of response was identified between patients that obtained a CR and PR (19.4 years versus 4.8 years, p < 0.0001). Non-hematological grade 3 or higher early toxicity was reported in 103 (20.1%) patients. Median OS was not reached: 95.3%, 92.4%, and 81.8% of patients were estimated to be alive at 5, 10, and 15 years, respectively. Forty-nine patients died (9.5%), following an infection in 14 cases (2.7%), natural causes in 14 (2.7%), cardiovascular events in 13 (2.5%), a second neoplasm in 6 (1.2%), and progression of HCL in 2 cases (0.4%). Following treatment of HCL with 2CDA, 80% of patients are estimated to be alive 15 years after diagnosis.
Re: Xiao et al.: Randomized controlled trial of a dichoptic digital therapeutic for amblyopia (Ophthalmology. 2022;129:77–85)
Authors: Mirjana Bjeloš, Zdenko Sonicki, Mladen Bušić, Ana Ćurić, Biljana Kuzmanović Elabjer
Journal: Ophthalmology (2022)
Radiogenomic analysis reveals tumor heterogeneity of triple-negative breast cancer
Authors: Lin Jiang, Chao You, Yi Xiao, He Wang, Guan-Hua Su, Bing-Qing Xia, Ren-Cheng Zheng, Dan-Dan Zhang, Yi-Zhou Jiang, Ya-Jia Gu, Zhi-Ming Shao
Journal: Cell Reports Medicine (2022)
Preinduced reovirus-specific T-cell immunity enhances the anticancer efficacy of reovirus therapy
Authors: Christianne Groeneveldt, Priscilla Kinderman, Jordi J C van Stigt Thans, Camilla Labrie, Lisa Griffioen, Marjolein Sluijter, Diana J M van den Wollenberg, Rob C Hoeben, Joke M M den Haan, Sjoerd H van der Burg, Thorbald van Hall, Nadine van Montfoort
Journal: Journal for ImmunoTherapy of Cancer (2022)

Background Many solid tumors do not respond to immunotherapy due to their immunologically cold tumor microenvironment (TME). We and others found that oncolytic viruses (OVs), including reovirus type 3 Dearing, can enhance the efficacy of immunotherapy by recruiting CD8 + T cells to the TME. A significant part of the incoming CD8 + T cells is directed toward reovirus itself, which may be detrimental to the efficacy of OVs. However, here we aim to exploit these incoming virus-specific T cells as anticancer effector cells. Methods We performed an in-depth characterization of the reovirus-induced T-cell response in immune-competent mice bearing pancreatic KPC3 tumors. The immunodominant CD8 + T-cell epitope of reovirus was identified using epitope prediction algorithms and peptide arrays, and the quantity and quality of reovirus-specific T cells after reovirus administration were assessed using high-dimensional flow cytometry. A synthetic long peptide (SLP)-based vaccination strategy was designed to enhance the intratumoral frequency of reovirus-specific CD8 + T cells. Results Reovirus administration did not induce tumor-specific T cells but rather induced high frequencies of reovirus-specific CD8 + T cells directed to the immunodominant epitope. Priming of reovirus-specific T cells required a low-frequent population of cross-presenting dendritic cells which was absent in Batf3 -/- mice. While intratumoral and intravenous reovirus administration induced equal systemic frequencies of reovirus-specific T cells, reovirus-specific T cells were highly enriched in the TME exclusively after intratumoral administration. Here, they displayed characteristics of potent effector cells with high expression of KLRG1, suggesting they may be responsive against local reovirus-infected cells. To exploit these reovirus-specific T cells as anticancer effector cells, we designed an SLP-based vaccination strategy to induce a strong T-cell response before virotherapy. These high frequencies of circulating reovirus-specific T cells were reactivated on intratumoral reovirus administration and significantly delayed tumor growth. Conclusions These findings provide proof of concept that OV-specific T cells, despite not being tumor-specific, can be exploited as potent effector cells for anticancer treatment when primed before virotherapy. This is an attractive strategy for low-immunogenic tumors lacking tumor-specific T cells.
The paradoxical promotion of ultraviolet tanning by US tanning salons offering a sunless option: A cross-sectional secret shopper study
Authors: Kayley L. Erickson, Sarah J. Eley, Cong Fan, Jatin Narang, Steve W. Gendi, Kelsey Ouyang, David X. Zheng, Jeremy S. Bordeaux
Journal: Journal of the American Academy of Dermatology (2022)
Neoadjuvant therapy gains FDA approval in non-small cell lung cancer
Authors: Ticiana A. Leal, Suresh S. Ramalingam
Journal: Cell Reports Medicine (2022)

Forde et al.1 reported on a randomized clinical trial (CheckMate 816) and showed that neoadjuvant therapy with nivolumab plus chemotherapy led to improved event-free survival and pathological complete response rate in patients with resectable non-small cell lung cancer (NSCLC).